Nuclear localization of hypoxia-inducible factor-2alpha in bovine arterial endothelial cells

Mol Cell Biol Res Commun. 1999 Aug;2(2):119-23. doi: 10.1006/mcbr.1999.0160.


Hypoxia-inducible factor (HIF)-2alpha is a recently identified hypoxia-inducible transcription factor abundantly expressed in vascular endothelial cells. As well as HIF-1alpha, HIF-2alpha forms a heterodimeric complex with the aryl hydrocarbon receptor nuclear translocator and upregulates hypoxia-inducible genes such as vascular endothelial growth factor. We found in this study that using green fluorescent protein (GFP) fusion constructs, the subcellular localization of HIF-2alpha was different from that of HIF-1alpha in bovine arterial endothelial cells (BAEC). HIF-1alpha was localized in the cytoplasm under normoxic cells and translocated from the cytoplasm into the nucleus in response to hypoxic induction. In contrast, HIF-2alpha was clearly localized in the nucleus of BAEC even under normoxic conditions. The regulation of HIF-2alpha might differ from that of HIF-1alpha in BAEC. We further showed that nuclear localization of HIF-2alpha was inhibited by either deletion or a single amino acid substitution within the C-terminal end of the protein. The amino acid sequence surrounding Lys737 and Arg738 functions as a nuclear localization signal of HIF-2alpha.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Amino Acid Substitution
  • Animals
  • Arteries / cytology
  • Base Sequence
  • Basic Helix-Loop-Helix Transcription Factors
  • Cattle
  • Cell Hypoxia
  • Cell Nucleus / metabolism*
  • Cells, Cultured
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism*
  • Green Fluorescent Proteins
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Molecular Sequence Data
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Trans-Activators*
  • Transcription Factors*


  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Luminescent Proteins
  • Nuclear Proteins
  • Recombinant Fusion Proteins
  • Trans-Activators
  • Transcription Factors
  • Green Fluorescent Proteins
  • endothelial PAS domain-containing protein 1